Department of Technology, Lianyungang Clinical College of Nanjing Medical University, Lianyungang, China.
Department of Technology, The First Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, China.
Immun Inflamm Dis. 2023 Jun;11(6):e881. doi: 10.1002/iid3.881.
Recent studies have demonstrated that exosomes play roles in pathogenesis and in the treatment of various diseases. We explored the influence of exosomes released from Talaromyces marneffei (T. marneffei)-infected macrophages on human macrophages to determine whether they play a role in the pathogenesis of T. marneffei infection.
Exosomes derived from macrophages infected with T. marneffei were extracted and characterized by transmission electron microscopy and western blot. Moreover, we examined exosomes that modulated IL-10 and TNF-α secretion and activation of p42 and p44 extracellular signal-regulated kinase 1 and 2 (ERK1/2) and activation of autophagy.
We found that exosomes promoted activation of ERK1/2 and autophagy, IL-10 and TNF-α secretion in human macrophages. Further, exosomes decreased the multiplication of T. marneffei in T. marneffei-infected human macrophages. Interestingly, exosomes isolated from T. marneffei-infected but not from uninfected macrophages can stimulate innate immune responses in resting macrophages.
Our studies are the first to demonstrate that exosomes isolated from T. marneffei-infected macrophages can modulate the immune system to control inflammation, and we hypothesize that exosomes play significant roles in activation of ERK1/2 and autophagy, the replication of T. marneffei and cytokine production during T. marneffei infection.
最近的研究表明，外泌体在各种疾病的发病机制和治疗中发挥作用。我们探讨了马尔尼菲篮状菌（Talaromyces marneffei，T. marneffei）感染的巨噬细胞释放的外泌体对人巨噬细胞的影响，以确定它们是否在 T. marneffei 感染的发病机制中发挥作用。
通过透射电子显微镜和 Western blot 提取和鉴定源自 T. marneffei 感染巨噬细胞的外泌体。此外，我们检测了调节 IL-10 和 TNF-α 分泌以及 p42 和 p44 细胞外信号调节激酶 1 和 2（ERK1/2）激活和自噬激活的外泌体。
我们发现外泌体促进了人巨噬细胞中 ERK1/2 和自噬、IL-10 和 TNF-α 的分泌。此外，外泌体还减少了 T. marneffei 在 T. marneffei 感染的人巨噬细胞中的增殖。有趣的是，源自 T. marneffei 感染而非未感染巨噬细胞的外泌体可以刺激静止巨噬细胞中的先天免疫反应。
我们的研究首次表明，源自 T. marneffei 感染巨噬细胞的外泌体可以调节免疫系统以控制炎症，我们假设外泌体在 T. marneffei 感染期间 ERK1/2 和自噬的激活、T. marneffei 的复制和细胞因子产生中发挥重要作用。
